Epidemiologic and scientific research indicates that diet and other lifestyle factors have a significant influence on the risk of developing colorectal cancer. Emerging data suggest some of these factors impact on the outcomes of patients with early stage colon cancer. However, there are no data on the influence of diet, lifestyle and other host factors on the outcomes of patients with more advanced colorectal cancer. At the time of initial diagnosis, 20% of colorectal cancer patients have evidence of metastases and another 15- 20% will recur with metastatic disease within a few years of initial diagnosis. In the past 10 years, there have been substantial improvements in chemotherapy options for these patients, with median survival exceeding 2 years and increasing number of patients living 4 or more years. Patients often seek to understand what, if any, diet and lifestyle will improve their outcomes, both survival and tolerability of therapy. Moreover, how diet and lifestyle influence prognosis may depend, in part, on molecular characteristics of the tumor. In response to a NIH Program Announcement, PA-09-148, "Studies of Energy Balance and Cancer in Humans," we propose to address these gaps in knowledge by utilizing data from 2 National Cancer Institute-sponsored chemotherapy trials in newly diagnosed patients with stage IV colorectal cancer (CALGB 80203 and 80405) which provide a) prospective assessments of diet, medication, lifestyle and comorbidities;b) paraffin-embedded tumor specimens to examine how such factors interact with specific molecular alterations;c) blood samples for research purposes;and d) comprehensive data on cancer progression, mortality, and chemotherapy-related toxicity. Since stage, performance status, use of combination chemotherapy and follow-up were carefully defined in this trial, residual confounding by disease characteristics and use of chemotherapy should be minimized. This database will provide the unique opportunity to examine the influence of energy balance (Aim 1), diet and vitamin D (Aim 2) and aspirin/NSAIDs (Aim 3) on the outcomes of patients with advanced colorectal cancer. Beyond the aforementioned hypotheses, this cohort will allow for the rapid examination of future hypotheses as they emerge. Ultimately, this database will permit us to ascertain the influence of numerous factors on colorectal cancer survival, improve our understanding of colorectal cancer biology, and potentially offer substantive diet and lifestyle recommendations for patients and health care providers. PUBLIC HEALTH RELEVANCE: Patients with cancer often seek information of diet and lifestyle as part of their therapy. Data generated from this application will help understand whether such factors influence the outcomes of patients. These data may influence treatment recommendations to future patients or lead to the development of a randomized trial to further knowledge in this area.